Histidine kinases are a key component of signal transduction in many organisms including bacteria, plants, fungi and yeast but not in mammalians, which makes histidine kinases excellent candidates as targets for a novel class of antibiotics. The knowledge of the three-dimensional structure of a histidine kinase will allow for the rational design of inhibitors with anti-microbial or anti-fungal properties. We have solved the crystal structure of the histidine kinase CheA involved in chemotaxis in bacteria. The structure comprises a dimerization domain, an ATP-binding domain and a regulatory domain. We plan to determine the structure of the ATP-binding domain in complex with an ATP-analog and the domain holding the substrate histidine.